1. Field of the Invention
The present invention relates to a group of bioinformatically detectable novel genes, here identified as “genomic address messenger” or “GAM” genes, which are believed to be related to the micro RNA (miRNA) group of genes.
2. Description of Prior Art
Over 300 small noncoding RNA's, termed Micro RNA's (miRNA's), have been identified to date in animals and plants (1-8). The MIR genes, code for ˜70-120 nt long non-protein-coding RNA sequences, that are the precursors of the ˜22 nt miRNA sequences, which in some cases, specifically inhibit translation of target genes, by complementary binding to their untranslated regions (UTR) (9-13). The first two MIR genes discovered, Lin-4 and Let-7, were found in the nematode Ceanorhabditis elegans, and shown to be involved in developmental timing (14, 15), hence originally called Short Temporal RNA (stRNA) (16). The ˜22 nt sequences inhibit translation of two respective target genes, Lin-14 and Lin-41, by complementary binding to their 3″ untranslated regions (UTR) (14, 17). Later studies by three separate groups (1-3) identified several precursor and mature miRNA's, some of them in clusters (1), expressed as sequences found in size fractionated (<80 nt) total RNA, in a wide spectrum of species, including C. elegans, Drosophila melanogaster, Homo sapiens, as well as plants. More recently, additional miRNA's from human (mir-91 to mir-121 (6)), mouse (mir-122 to mir-155 (4)) and plants (mir-156 to mir-171 (5)), have been reported. Furthermore, Llave et al identified in Arabidopsis thaliana 125 sequences, 21-24 nucleotides in length and presumably miRNAs (8). Each of the MIR genes is transcribed and processed to an ˜80 nt-long hairpin shaped miRNA precursor, which is then processed by an enzyme called Dicer, to yield the mature ˜22 nt-long single stranded miRNA. Such small RNAs will inhibit translation of target genes by complementary binding to sites in the 3″ or 5″ untranslated regions (18). Their structural similarity to the two well-studied miRNA's in C. elegans, Lin-4 and Let-7, supports the belief that MIR genes code for specific translation inhibitors of target genes. However, determining the targets of the miRNAs is more complicated than just searching for antisense complementarity, because bulges and loops, disrupting perfect complementarity, are not only tolerated, but seem to be the rule in the postulated binding between the miRNA's and their target UTR's (19). Target-gene binding sites of most reported miRNA's, except of Lin-4 and Let-7, have not been found, and therefore the specific functionality of these genes is still unknown. Using a computational approach, Rhoades et al (19), predicted targets for 14 A. thaliana miRNA's by identifying their near complementarity to the predicted targets. However, using the same approach was not helpful in identifying miRNA targets in C. elegans and D. melanogaster, raising the possibility that the near-perfect complementarity appears to be specific to plants (19).
The ability to detect novel RNA genes is limited by the methodologies used to detect such genes. All RNA genes identified so far either present a visibly discernable whole body phenotype, as do Lin-4 and Let-7 (Wightman et. al., Cell 75, 855 (1993); Reinhart et al., Nature 403, 901 (2000)), or produce significant enough quantities of RNA so as to be detected by the standard biochemical genomic techniques, as do the 93 recently detected miRNA genes.  Since a limited number clones were sequenced by the researchers discovering these genes, 300 by Bartel and 100 by Tuschl (Bartel et. al., Science 294, 858 (2001); Tuschl et. al., Science 294, 853 (2001)), the RNA genes found can not be much rarer than 1% of all RNA genes. The recently detected miRNA genes therefore represent the more prevalent among the miRNA gene family.
Current methodology has therefore been unable to detect RNA genes which either do not present a visually discernable whole body phenotype, or are rare (e.g. rarer than 0.1% of all RNA genes), and therefore do not produce significant enough quantities of RNA so as to be detected by standard biochemical technique.